Signalling dynamics in the spindle checkpoint response

Nat Rev Mol Cell Biol. 2014 Nov;15(11):736-47. doi: 10.1038/nrm3888. Epub 2014 Oct 10.


The spindle checkpoint ensures proper chromosome segregation during cell division. Unravelling checkpoint signalling has been a long-standing challenge owing to the complexity of the structures and forces that regulate chromosome segregation. New reports have now substantially advanced our understanding of checkpoint signalling mechanisms at the kinetochore, the structure that connects microtubules and chromatin. In contrast to the traditional view of a binary checkpoint response - either completely on or off - new findings indicate that the checkpoint response strength is variable. This revised perspective provides insight into how checkpoint bypass can lead to aneuploidy and informs strategies to exploit these errors for cancer treatments.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aneuploidy
  • Cell Cycle Checkpoints*
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Transformation, Neoplastic
  • Chromosome Segregation
  • Chromosomes / metabolism*
  • Chromosomes / ultrastructure
  • Gene Expression Regulation
  • Humans
  • Kinetochores / metabolism
  • Kinetochores / ultrastructure
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Mitosis*
  • Protein Binding
  • Signal Transduction
  • Spatio-Temporal Analysis
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure


  • Cell Cycle Proteins